Clinical Study to Evaluate the Safety, Immunogenicity and Efficacy of Investigational Flu Vaccine Compared to Approved Flu Vaccine in Children.

Phase 3

Completed

Conditions: Influenza Virus

Registration Number: NCT01964989

Lead Sponsor: Seqirus

Brief Summary: Safety, Immunogenicity and Efficacy of an Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine Compared to Non-Adjuvanted Comparator Influenza Vaccine in Children ≥6 to \<72 Months of Age. The study was conducted during the 2013/2014 and 2014/2015 northern hemisphere influenza season.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10644

Inclusion Criteria

Children, males and females, healthy or at high risk of complications from influenza, between ≥6 months to <72 months of age
Documented consent provided by the subject's parent(s)/legal guardian(s)
Subjects and/or subject's parent(s)/legal guardian(s) able to comply with all study procedures.

Exclusion Criteria

Children with history of allergy to vaccine components.
Additional eligibility criteria may be discussed by contacting the site

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Efficacy Endpoint: First-Occurrence Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months of Age	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects ≥6 to \<72 months of age with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).

Secondary Outcome Measures

Name	Time	Method
Efficacy Endpoint: First-Occurrence RT-PCR Confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <24 Months, ≥6 to <36 Months and ≥36 to <72 Months of Age.	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).
Efficacy Endpoint: First-Occurrence Culture Confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months, ≥6 to <24 Months, ≥6 to <36 Months and ≥36 to <72 Months of Age	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects with culture confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).
Efficacy Endpoint: First-occurrence RT-PCR and Culture Confirmed Influenza A and/or B of Any Influenza Strain in Subjects at High Risk of Influenza Complications	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects ≥6 to \<72 months of age with RT-PCR confirmed and culture confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer, in healthy subjects and subjects at risk of influenza related complications. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).
Efficacy Endpoint: First-occurrence RT-PCR and Culture Confirmed Influenza A and/or B of Any Influenza Strain in Naive and Non-naive Subjects Separately	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).
Efficacy Endpoint: First-occurrence RT-PCR-confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months of Age at ≥7 Days and at ≥14 Days After First Vaccination up to the Day of Second Vaccination in Vaccine naïve Subjects Only	≥7 days and at ≥14 days after first vaccination up to day of second vaccination	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was based on the number of vaccine naive subjects ≥6 to \<72 months of age with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥7 days and ≥14 days after the first vaccination up to the day of the second vaccination. TIV was used as the comparator in Season 1; and QIV was used as the comparator in Season 2. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).
Immunogenicity Endpoint: Hemagglutination Inhibition (HI) Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Geometric Mean Titers (GMTs) and GMT Ratios in Subjects ≥6 to <72 Months of Age	Baseline (Day 1), Day 29, Day 50 and Day 209 for vaccine naïve subjects; Baseline (Day 1), Day 22 and Day 181 for vaccine non-naïve subjects	Pooled GMT values across both naïve and non-naïve subjects are provided for the Day 22/50 (ie, 21 days after last vaccination) and Day 181/209 (ie, 180 days after last vaccination) assessments; Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/ Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine comparison analysis.
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms GMT and GMT Ratios at 21 Days After Last Vaccination in Healthy vs High Risk Subjects ≥6 to <72 Months of Age	Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)	HI GMT was assessed on Day 1 and Day 50 for vaccine naïve healthy vs high risk subjects; and HI GMT were assessed on Day 1 and Day 22 for vaccine non-naïve healthy vs high risk subjects; pooled GMT values across both naïve and non-naïve subjects are provided for Day 22/50 (ie, 21 days after last vaccination) assessments.
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Geometric Mean Ratios (GMR) in Subjects ≥6 to <72 Months of Age	Baseline (Day 1), Day 29, Day 50 and Day 209 for vaccine naïve subjects; Baseline (Day 1), Day 22 and Day 181 for vaccine non-naïve subjects	The fold-increase in HI antibodies in response to vaccination was assessed as the GMR between all post-vaccination titers (ie, Day 29, 50, 209 for vaccine naïve subjects; Day 22, 181 for vaccine non-naïve subjects) and the baseline (Day 1) titer. Assessed GMRs thus correspond to Day 29/Day 1, Day 50/Day 1, and Day 209/Day 1 for vaccine naïve subjects and Day 22/Day 1 and Day 181/Day 1 for vaccine non-naïve subjects. Pooled GMR values across both naïve and non-naïve subjects are provided for Day (22/50)/Day 1 (ie, 21 days after last vaccination) and Day (181/209)/Day 1 (ie, 180 days after last vaccination); Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine comparison analysis.
Safety Endpoint: Number of Subjects With Solicited Local and Systemic AEs	7 days following each vaccination	Subjects ≥6 to \<72 months of age reporting solicited local and systemic reactions, day 1 to day 7 after vaccination with either aQIV or TIV/QIV.
Safety Endpoint: Number of Subjects With Unsolicited AEs, SAEs, AEs Leading to Withdrawal From the Study or Study Vaccination, NOCDs and AESIs	Day 1 though Day 366 (vaccine non-naive)/Day 390 (vaccine naive)	Safety was assessed in terms of number of subjects ≥6 to \<72 months of age reporting unsolicited reactions (Day 1 to Day 50 for vaccine naïve subjects and from Day 1 to Day 22 for vaccine non-naïve subjects); Serious Adverse Events (SAEs), AEs leading to New Onset of Chronic Diseases,(NOCD), Adverse Events of Special Interests (AESI), AEs leading to withdrawal from the study or study vaccination after vaccination with either aQIV or TIV/QIV were collected up to 12 months after last vaccination.
Healthcare Utilization and Health Economic Endpoints: Number of Days of Daycare, School or Preschool Missed by Subjects Associated With RT-PCR-confirmed Influenza	within a window of 14 days after influenza-like illness (ILI)-onset
Efficacy Endpoint: First-occurrence RT-PCR-confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months of Age Occurring at ≥7 Days and ≤21 Days After Last Vaccination, in All Subjects.	≥7 days and ≤21 days after the last vaccination	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was based on the number of vaccine naïve subjects ≥6 to \<72 months of age with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥7 days and ≤21 after the last vaccination. TIV was used as the comparator in Season 1; and QIV was used as the comparator in Season 2. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Seroconversion (SC) Rates and Difference in SC Rates at 21 Days in Subjects ≥6 to <72 Months of Age	Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)	SC rates were assessed on Day 1 and Day 50 (ie, 21 days after two vaccinations) for vaccine naïve subjects; and on Day 1 and Day 22 (ie, 21 days after one vaccination) for vaccine non-naïve subjects; values pooled across naive and non-naive subjects are provided. Seroconversion is defined as HI ≥ 1:40 for subjects negative at baseline (ie, HI titer\<1:10); or a minimum 4-fold increase in HI titer for subjects positive at baseline (ie, HI titer ≥ 1:10); Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strain: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine. comparison analysis (N=745 for aQIV, N=738 for comparator).
Immunogenicity Endpoint: Hemagglutination Inhibition (HI) Antibody Responses to aQIV vs TIV/QIV Against Heterologous Strains in Terms of Geometric Mean Titers (GMTs) in Subjects ≥6 to <72 Months of Age	21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)	HI GMT was assessed 21 days after last vaccination (Day 50 for vaccine naïve subjects and Day 22 for vaccine non-naive subjects) pooled GMT values across both naïve and non-naïve subjects are provided for the Day 22/50 (ie, 21 days after last vaccination); Heterologous strains: H1N1=A/Brisbane/59/2007- like; H3N2 =A/Hong Kong/4801/2014; B/Yamagata=B/Phuket/3073/2013-like; B Victoria=B/Malaysia/2506/2004; For B/Victoria results from Season 2 only are presented for both vaccine groups.
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Heterologous Strains in Terms of Percentage of Subjects With HI Titer ≥ 1:40 in Subjects ≥6 to <72 Months of Age	21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)	Antibody persistence was assessed as the percentage of subjects with HI titer of ≥1:40 at 21 days after last vaccination (ie, Day 50 for vaccine naïve subjects and Day 22 for vaccine non-naïve subjects). Results were then pooled across both vaccine naïve and non-naïve subjects; Heterologous strains: H1N1=A/Brisbane/59/2007- like; H3N2 =A/Hong Kong/4801/2014; B/Yamagata=B/Phuket/3073/2013- like; B Victoria=B/Malaysia/2506/2004; For B/Victoria results from Season 2 only are presented for both vaccine groups.
Healthcare Utilization and Health Economic Endpoint: Number of Medical Visit for Respiratory Illness Associated With RT-PCR-confirmed Influenza	within a window of 14 days after ILI-onset
Healthcare Utilization and Health Economic Endpoint: Number of Employment Days Missed by Parent(s)/Guardian(s) of Subjects With RT-PCR-confirmed Influenza	within a window of 14 days after ILI-onset
Healthcare Utilization and Health Economic Endpoint: First-occurrence of RT-PCR-confirmed Moderate-to-severe Influenza Cases as Per Prespecified Criteria in Subjects ≥6 to <72 Months of Age in Season 2.	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Geometric Mean Titers (GMTs) in Vaccine Naive Subjects ≥6 to <72 Months of Age	Day 29 and Day 50	GMTs for vaccine naïve subjects are provided by strain for Day 29 and Day 50; Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/ Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine comparison analysis.
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Percentage of Subjects With HI Titer ≥ 1:40 and Percentage Differences at 180 Days After Last Vaccination in Subjects ≥6 to <72 Months of Age	Baseline (Day 1) and 180 days after the last vaccination (Day 209 for vaccine naive subjects; Day 181 for vaccine non-naïve subjects)	Antibody response was assessed as the percentage of subjects with HI titer of ≥1:40 at 180 days after last vaccination (ie, Day 209 for vaccine naïve subjects and Day 181 for vaccine non-naïve subjects). Results were then pooled across both vaccine naïve and non-naïve subjects. Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; B/Victoria results from Season 1 and Season 2 (aQIV) and Season 2 (comparator) are presented.
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Percentage of Subjects With HI Titers ≥1:110, ≥1:151, ≥1:215, ≥1:330, and ≥1:629 in Subjects ≥6 to <72 Months of Age	Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)	Antibody response was assessed as the percentage of subjects and differences of percentage of subjects with HI titers of ≥1:110, ≥1:151, ≥1:215, ≥1:330, and ≥1:629 at 21 days after last vaccination (ie, Day 50 for vaccine naïve subjects and Day 22 for vaccine non-naïve subjects). Results were then pooled across both vaccine naïve and non-naïve subjects. Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; B/Victoria results from Season 1 and Season 2 (aQIV) and Season 2 (comparator) are presented.
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Heterologous Strains in Terms of Seroconversion (SC) Rates in Subjects ≥6 to <72 Months of Age	21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)	SC rates were assessed on Day 50 (ie, 21 days after two vaccinations) for vaccine naïve subjects; and on Day 22 (ie, 21 days after one vaccination) for vaccine non-naïve subjects; values pooled across naive and non-naive subjects are provided. Seroconversion is defined as HI ≥ 1:40 for subjects negative at baseline (ie, HI titer\<1:10); or a minimum 4-fold increase in HI titer for subjects positive at baseline (ie, HI titer ≥ 1:10); Heterologous strains include: H1N1=A/Brisbane/59/2007- like; H3N2 =A/Hong Kong/4801/2014; B/Yamagata=B/Phuket/3073/2013- like; B Victoria=B/Malaysia/2506/2004; For B/Victoria results from Season 2 only are presented for both vaccine groups

Trial Locations

Locations (167): 222, Novartis Investigational Site
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Chandler, Arizona, United States
267, Novartis Investigational Site
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Harrisburg, Arkansas, United States
259, Novartis Investigational Site
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Anaheim, California, United States
280, Novartis Investigational Site
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Anaheim, California, United States
213, Novartis Investigational Site
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Baldwin Park, California, United States
407, Novartis Investigational Site
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Downey, California, United States
238, Novartis Investigational Site
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La Puente, California, United States
411, Novartis Investigational Site
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Ontario, California, United States
202, Novartis Investigational Site
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Paramount, California, United States
250, Novartis Investigational Site
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San Diego, California, United States
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222, Novartis Investigational Site
🇺🇸Chandler, Arizona, United States